VAV-1 acts in a single interneuron to inhibit motor circuit activity in Caenorhabditis elegans

Nat Commun. 2014 Nov 21;5:5579. doi: 10.1038/ncomms6579.

Abstract

The complex molecular and cellular mechanisms underlying neuronal control of animal movement are not well understood. Locomotion of Caenorhabditis elegans is mediated by a neuronal circuit that produces coordinated sinusoidal movement. Here we utilize this simple, yet elegant, behaviour to show that VAV-1, a conserved guanine nucleotide exchange factor for Rho-family GTPases, negatively regulates motor circuit activity and the rate of locomotion. While vav-1 is expressed in a small subset of neurons, we find that VAV-1 function is required in a single interneuron, ALA, to regulate motor neuron circuit activity. Furthermore, we show by genetic and optogenetic manipulation of ALA that VAV-1 is required for the excitation and activation of this neuron. We find that ALA signalling inhibits command interneuron activity by abrogating excitatory signalling in the command interneurons, which is responsible for promoting motor neuron circuit activity. Together, our data describe a novel neuromodulatory role for VAV-1-dependent signalling in the regulation of motor circuit activity and locomotion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aldicarb / pharmacology
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / biosynthesis
  • Caenorhabditis elegans Proteins / genetics*
  • Cholinergic Agonists / pharmacology
  • Cholinesterase Inhibitors / pharmacology
  • GABA Antagonists / pharmacology
  • Interneurons / metabolism*
  • Levamisole / pharmacology
  • Locomotion / genetics
  • Locomotion / physiology*
  • Motor Activity / genetics
  • Motor Activity / physiology*
  • Motor Neurons / metabolism
  • Nerve Tissue Proteins / biosynthesis
  • Paralysis / chemically induced
  • Pentylenetetrazole / pharmacology
  • Proto-Oncogene Proteins c-vav / biosynthesis
  • Proto-Oncogene Proteins c-vav / genetics*
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, Cholinergic
  • Rho Guanine Nucleotide Exchange Factors
  • Rhodopsin / biosynthesis
  • Signal Transduction

Substances

  • Caenorhabditis elegans Proteins
  • Cholinergic Agonists
  • Cholinesterase Inhibitors
  • GABA Antagonists
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-vav
  • RNA, Small Interfering
  • Receptors, Cholinergic
  • Rho Guanine Nucleotide Exchange Factors
  • VAV-1 protein, C elegans
  • Levamisole
  • Aldicarb
  • Rhodopsin
  • Pentylenetetrazole